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In this study, extremely preterm infants didn't benefit more from noninvasive ventilation using intermittent rather than continuous positive airway pressure.

Note that the study suggests that although limiting mechanical injury to the lungs is important, additional therapeutic strategies are needed for infants with extremely immature lungs.

Extremely preterm infants got no more benefit from noninvasive ventilation with intermittent than with continuous positive airway pressure, the NIPPV trial showed.

No clinically important outcomes differed significantly between nasal intermittent positive-pressure ventilation (IPPV) and nasal continuous positive airway pressure (CPAP) for the high-risk group of infants born before 30 weeks' gestation at a weight less than 1,000 g (2.2 lb), Haresh Kirpalani, BM, MSc, of the Children's Hospital of Philadelphia, and colleagues found.

But the confidence interval was wide, suggesting anywhere from a 21% reduction to a 35% increase in that risk with nasal IPPV versus nasal CPAP, they noted.

"These findings call into question the current widespread use of nasal IPPV," they wrote, noting that it is more complicated and more expensive than what they called the current standard of care, nasal CPAP.

Some prior trials and meta-analyses had suggested promise with nasal IPPV (which superimposes an intermittent peak pressure on CPAP), but most were single-center and enrolled larger infants, who have lower risk of bronchopulmonary dysplasia.

"We speculate that although limiting mechanical injury is important, additional therapeutic strategies are needed for infants with extremely immature lungs," Kirpalani's group noted.

Given the conflicting evidence, the NIPPV trial was valuable in providing some solid ground for clinicians, commented F. Sessions Cole, MD, director of newborn medicine at Missouri's St. Louis Children's Hospital.

It "provides the clinician a choice for individualizing these breathing support strategies for each infant based on a sound randomized clinical trial," he told MedPage Today.

"Thanks to the 'pragmatic' investigative strategy of this trial -- multiple international centers, considerable clinician choice -- this study provides a real-world assessment that is applicable to a common problem (respiratory failure) in very premature infants," he added in an email. "Its results are thus easily translatable to clinical practice."

However, Joshua Petrikin, MD, a neonatologist with Children's Mercy Hospitals and Clinics in Kansas City, Mo., was more skeptical that the findings would do much to further practice.

The trial was powered to detect a 20% reduction in death or bronchopulmonary dysplasia with IPPV, which "seems designed to not find a difference," he said in an email to MedPage Today. "A 20% reduction would be a phenomenal finding in this population."

For the primary composite endpoint of death before 36 weeks of postmenstrual age or survival with bronchopulmonary dysplasia at 36 weeks of postmenstrual age, the rate was 38.4% with nasal IPPV versus 36.7% with nasal CPAP (P=0.56).

Additional adjustment for sex, use of antenatal glucocorticoids, and use of caffeine did little to change the odds ratio (1.05, 95% CI 0.80 to 1.39).

Duration of respiratory support (postmenstrual age at last support 36.9 versus 36.7 weeks, P=0.59)

Time to full feedings (17 versus 16 days, P=0.37)

Subgroup analyses showed no interactions with birth weight, prior intubation, or use of synchronized nasal IPPV.

Limitations included lack of blinding, which may have introduced bias despite guidelines in the protocol for weaning, extubation, and reintubation, as well as no specification of the ventilator device or synchronization in the protocol or data on surfactant use.

Because of the "mass variation in the management of patients on CPAP relating to the beliefs of the practitioners, the training and availability of the nursing staff, the culture of the unit, etc., that greatly effect the efficacy" of these ventilation strategies, Petrikin argued that the study likely had too few patients to average out the multitude of variables involved.

He also highlighted the 10% of CPAP patients who got IPPV in error, the one-third of approached eligible patients not enrolled, that high-flow nasal cannulas were not allowed, and the high rate of reintubation at nearly 60% in both groups.

Cole added that long-term outcomes for these babies will need to be followed to see if differences emerge later.

UPDATE: This article, originally published Aug, 14, 2013 at 5:00 p.m. was updated with new material (Aug, 14, 2013 at 7:45 p.m.).

The study was funded by the Canadian Institutes of Health Research.

Kirpalani reported receiving grant and travel support money to his institution from the Canadian Institutes of Health Research.

Crystal Phend joined MedPage Today in 2006 after roaming conference halls for publications including The Medical Post, Oncology Times, Doctor's Guide, and the journal IDrugs. When not covering medical meetings, she writes from Silicon Valley, just south of the San Francisco fog.

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